The studies to be conducted under this grant fall in four major areas: 1) complete work on the total synthesis of the hypoglycemic agent Saudin (1); test 1 and its precursors to identify the pharmacophore, and determine if possible the mechanism by which the hypoglycemic effects are elicited (in collaboration with Sandoz Research Institute); prepare appropriate analogues as warranted by the preceding studies; 2) continue work directed at the application of Lewis acid catalyzed asymmetric [2+2] cycloaddition reactions to (+)-Laurencin (2) and Laurenyne (3) which employs a novel retro-Claisen rearrangement to create the required oxocene ring system in enantiomerically pure form; 3) continue preliminary studies begun recently directed toward the preparation of the novel squalene synthetase inhibitor (+)-Zaragozic Acid C, one of a group of novel antifungal enzyme inhibitors known as the squalestatins 1-3 and the Zaracozic Acids A-C isolated by Glaxo and Merck groups. The approach utilizes a novel application of a net [4-3] cycloaddition to construct the core of the novel squalene synthetase inhibitor Zaragozic Acid C (4); and, 4) initiate synthetic studies directed toward UCT4B (6), a recently characterized DNA gyrase inhibitor, which holds promise as both an antibiotic and a potentially antitumor agent. UCT4B (6) is a member of a small but growing group of biologically active diterpene derivatives which also includes Clerocidin and Terpenticin. A novel protection scheme employing a chiral diol acetal is envisioned to permit control over the key asymmetric centers present in the acyclic chain and provide convenient access to an immediate precursor of the sensitive alpha-ketoaldehyde unit.